Chronic wounds represent a major health burden world-wide, and a significant drain on medical resources. For example, recent studies have calculated the annual cost of chronic wounds to the NHS in the United Kingdom to be approximately £1 billion (Harding, “The Future of Wound Healing,” In: Leaper et al., Wounds: Biology and Management,” Oxford University Press, 1998 at page 191). Foot ulceration, the most common complication of diabetes requiring hospitalization, is estimated to cost the UK approximately £17 million per year (Currie et al., 1998, Diabetes Care 21:42-48) and the US approximately $150 million per year (Reiber et al., 1992, Diabetes Care 15(suppl. 1):29-31). The total annual cost of diabetic peripheral neuropathy and its complications in the US was estimated to be between $4.6 and $13.7 billion (Gordois, et al., 2003, Diabetes Care 26:1790-1795). Equally, or even more costly are managing and treating pressure ulcers (bed sores)—$55 billion annually—and venous leg ulcers—estimated to be 2.5 to 3 billion US dollars, with a loss of 2 million work days per year (McGuckin, et al., 2001, Adv Skin Wound Care 14(1):33-36; and see decubitus.org/cost/cost.html).
These sums show only the economic costs of managing and treating chronic wounds. They do not reflect the frustration, economic loss and impaired quality of life experienced by patients with chronic wounds. Indeed, deep foot ulcers may be accompanied by cellulites or osteomyelitis, and a severely infected or nonhealing foot ulcer may require amputation of the toe, foot or leg (Gordois, et al., 2003, Diabetes Care 26:1790-1795).
Recent understandings of the biology underlying wound healing have led to the development of several new and experimental treatments. These include: the use of dressings designed to promote wound healing; topical administration of growth factors such as transforming growth factor beta, which is currently being studied for use in venous ulcers, platelet derived growth factor, which has been licensed for the treatment of diabetic foot ulcers (becaplermin, Regranex) and has shown some promise in treating pressure ulcers (Rees, 1997, Wound Repair Regen. 7:141-147), granulocyte colony stimulating factor, which has been evaluated for the treatment of infected diabetic foot ulcers (Gough, 1997, Lancet 350:833-859), fibroblast growth factor, which has been assessed for treating pressure ulcers (Robson et al., 1992, Ann. Surg. 216(40):401-408), and epidermal growth factor, which has been used to treat venous leg ulcers (Falanga et al., 1992, J. Dermatol. Surg. Oncol. 18:604-606); autologous skin grafts, which have been successfully used to treat venous leg ulcers (Mauro, T. M., 1992, West J. Med. 156(2): 191); and bioengineered skin equivalents such as Alloderm (a dermal matrix without immunogenic cells), Integra (a combination of dermal fibroblasts and bovine collagen), Dermagraft (non-immunogenic neonatal fibroblasts cultured in a polyglactin mesh) and Apilgraf (contains both epidermal and dermal components). All of these bioengineered skin grafts have been used to treat burns. Dermagraft has also been used to treat diabetic foot ulcers (Gentzkow et al., 1996, Diabetes Care 19:350-354). Apilgraf has been used to treat diabetic foot ulcers (Veves et al., 2001, Diabetes Care 24:290-295) and venous leg ulcers (Falanga et al., 1998, Arch. Dermatol. 134:293-300).
Unfortunately, clinical results with these new technologies have not been as dramatic as hoped. Accordingly, there remains a need in the art for new strategies and compositions for the treatment of wounds generally, and chronic wounds specifically.